The overall objective of this project is to elucidate the ways in which the ventilatory response to hypoxia may be altered by disease states. The emphasis is upon study of those components of the response to hypoxia which do not directly involve the peripheral arterial chemoreceptors. Thus a major goal is to describe and determine the mechanisms of the ventilatory responses to central nervous system hypoxia. The methodologic approach will be to develop and study animal models of disease states in which there are varying degrees of deprivation of oxygen delivery to the brain. These will include: severe anemia, carboxyhemoglobinemia, direct impairment of brain blood flow and certain forms of cerebral edema. The studies will involve measurement of brain blood flow as well as indices of oxygenation, acid-base balance and metabolic rate in cerebral venous blood and cerebralspinal fluid. These will be correlated to ventilatory responses. BIBLIOGRAPHIC REFERENCES: The effect of anemia on the ventilatory response to transient and steady-state hypoxia. T.V. Santiago, N.H. Edelman, and A.P. Fishman. J. Clin. Invest. 55:410-418, 1975. The mechanism of the ventilatory response to carbon monoxide of unanesthetized goats. N.H. Edelman, T.V. Santiago, D. Doblar. Proceedings of Krough Centenary Symposium (in press).